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Search Results to Charles Louis Edelstein

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One or more keywords matched the following properties of Edelstein, Charles

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overview My NIH-funded research from 2001-2007 investigated caspases and apoptosis in PKD. We demonstrated that both pharmacologic (caspase inhibitor) and genetic (double knockout caspase-3 cpk/cpk mice) methods of apoptosis inhibition resulted in less apoptosis and proliferation and less PKD. My NIH-funded research from 2008 to 2012 investigated mTORC1 signaling in PKD and we were first to demonstrate that sirolimus attenuates PKD in rat and mouse models. Recently we published the first report of decreased autophagy in polycystic kidneys of cpk mice and Han:SPRD rats. Based on our published and preliminary data and the fact that many of the agents that protect against PKD are autophagy inducers, we developed the hypothesis that PKD is a state of decreased autophagy. We also hypothesized that autophagy inhibition would reverse the protective effect against PKD of known autophagy inducers like caloric restriction, metformin. My grant to study autophagy in PKD is funded by the Dept. of Veteran’s Affairs. My Dept. of Defense funding (2015-2019) was to study novel mTORC1 and 2 pathways in PKD kidneys. We were first to demonstrate that the second generation mTOR inhibitors, the mTOR kinase inhibitors, attenuate PKD in a rat model and that an mTOR antisense that targets both mTORC1 and 2 also attenuates PKD in a Pkd2 knockout mouse model. Cardiac disease is the commonest cause of death in PKD. During our studies of mTOR in PKD kidneys, we noticed enlarged hearts in 5 rodent models of PKD and increased mTORC1/2 signaling in the heart in Pkd1 knockout mice. These data led us to the Aims for the Dept. of Defense Award to determine the effect of genetic or pharmacological inhibition of mTORC1 (4E-BP1) or mTORC2 on cardiac structure and function and mTORC1/2 signaling in the heart in mice with PKD. Our published studies demonstrate the therapeutic effect of sirolimus, ACE inhibitors and statins, VEGFR inhibitors, caspase inhibitors, combined mTORC1 and 2 inhibition, angiotensinogen inhibition, mTOR kinase inhibitors and lack of therapeutic effect of HIF-1 inhibitors in animal models of PKD. These studies demonstrate our expertise in performing therapeutic studies in animal models of PKD. Cysteine proteases and IL-18 in acute kidney injury (AKI) In 1995 we were the first to describe the role of the cysteine protease, calpain, in AKI. In the late 1990s a group of cysteine proteases called caspases, that mediated programmed cell death or apoptosis, were discovered. I received NIH funding to study the role of cysteine proteases in AKI. I focused on caspase-1, also known as Interleukin-1 converting enzyme or ICE, that activates the cytokines IL-1 and IL-18. In two papers in J. Clin. Invest. in 2001 and 2002, we described that IL-18 was both a mediator and biomarker of AKI. I received renewal of my NIH funding to continue the study of IL-18 in experimental AKI. I demonstrated the mechanisms of IL-18-mediated kidney injury and the source of IL-18 in the kidney. Recently, we discovered that IL-33, another IL-1 family cytokine that is activated by caspases, is a mediator of cisplatin-induced AKI. The studies of IL-33 in AKI were funded as a VA Merit Award in 2012 continuing over 10 years of NIH funding of our work on cysteine proteases in AKI. Biomarkers of AKI Our mouse studies in 2001 that IL-18 increases in the kidney and urine in AKI were the first suggestion of the use of biomarkers that come from the kidney to diagnose AKI rather than serum creatinine that has been used since 1917. The IL-18 work was taken to the bedside and we received a patent in 2006 for IL-18 as a biomarker of AKI in humans. We demonstrated that IL-18 is an early biomarker of AKI in patients with delayed graft function and patients post cardiac surgery. I helped establish and was Co-Investigator of an NIH-funded consortium, the Translational Research involving Biomarkers of Early AKI Consortium (TRIBE-AKI),that performed and published multiple clinical studies of biomarkers, including IL-18, as an alternative to creatinine, in diagnosing AKI. The largest AKI biomarker study ever performed of over 1200 patients demonstrated that urine IL-18, urine and plasma NGAL were early biomarkers of AKI and increased before creatinine in patients with AKI. We demonstrated that the biomarkers of AKI in humans go up within 6 hours of the kidney injury and 2 days before serum creatinine. In 2010 (first Edition) and 2017 (Second Edition), I edited a book “Biomarkers in Kidney Diseases”, that included the novel AKI biomarker work. In summary, I have made original discoveries on the role of the cysteine proteases and cysteine protease-derived cytokines in both PKD and AKI. I was the first to suggest that biomarkers like IL-18, that are made by the kidney, may be more promising than creatinine, the conventional way to diagnose AKI. Both our IL-18 biomarker studies in AKI and our mTOR studies in PKD have been translated to the bedside.

One or more keywords matched the following items that are connected to Edelstein, Charles

Item TypeName
Academic Article Urinary interleukin-18 is a marker of human acute tubular necrosis.
Academic Article Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney.
Academic Article Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury.
Academic Article Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice.
Academic Article Role of caspases in hypoxia-induced necrosis of rat renal proximal tubules.
Academic Article Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery.
Academic Article Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function.
Academic Article IL-33 exacerbates acute kidney injury.
Academic Article Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury.
Academic Article Some biomarkers of acute kidney injury are increased in pre-renal acute injury.
Academic Article Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice.
Academic Article Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice.
Academic Article Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation.
Academic Article Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice.
Academic Article Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery.
Academic Article Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation.
Academic Article Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit.
Academic Article Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure.
Academic Article Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury.
Academic Article Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study.
Academic Article Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children.
Academic Article Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery.
Academic Article Depletion of macrophages and dendritic cells in ischemic acute kidney injury.
Concept Interleukin-1alpha
Concept Interleukin-1
Concept Interleukin 1 Receptor Antagonist Protein
Concept Interleukin-10
Concept Interleukin-1beta
Concept Receptors, Interleukin-8B
Concept Interleukin-8
Concept Interleukin-6
Concept Interleukin-18
Concept Interleukin-12
Academic Article NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury.
Academic Article Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.
Academic Article Pathophysiology of cisplatin-induced acute kidney injury.
Academic Article Antisense-mediated angiotensinogen inhibition slows polycystic kidney disease in mice with a targeted mutation in Pkd2.
Academic Article A pan caspase inhibitor decreases caspase-1, IL-1a and IL-1ß, and protects against necrosis of cisplatin-treated freshly isolated proximal tubules.
Academic Article Increased levels of soluble ST2 in patients with active newly diagnosed ANCA-associated vasculitis.
Academic Article NF-?B transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI).
Grant Caspase-1 signaling in ischemic acute renal failure
Grant The IL-33/CD4 T cell/CXCL1 System in Acute Kidney Injury
Academic Article Catheter-based renal sympathetic denervation induces acute renal inflammation through activation of caspase-1 and NLRP3 inflammasome.
Academic Article Biomarkers of Drug-Induced Kidney Toxicity.
Concept Interleukin-33
Concept Interleukin-1 Receptor-Like 1 Protein
Academic Article IL-6-mediated hepatocyte production is the primary source of plasma and urine neutrophil gelatinase-associated lipocalin during acute kidney injury.

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